Oncoprotein DEK as a tissue and urinary biomarker for bladder cancer

<p>Abstract</p> <p>Background</p> <p>Bladder cancer is a significant healthcare problem in the United States of America with a high recurrence rate. Early detection of bladder cancer is essential for removing the tumor with preservation of the bladder, avoiding metastasis and hence improving prognosis and long-term survival. The objective of this study was to analyze the presence of DEK protein in voided urine of bladder cancer patients as a urine-based bladder cancer diagnostic test.</p> <p>Methods</p> <p>We examined the expression of DEK protein by western blot in 38 paired transitional cell carcinoma (TCC) bladder tumor tissues and adjacent normal tissue. The presence of DEK protein in voided urine was analyzed by western blot in 42 urine samples collected from patients with active TCC, other malignant urogenital disease and healthy individuals.</p> <p>Results</p> <p>The DEK protein is expressed in 33 of 38 bladder tumor tissues with no expression in adjacent normal tissue. Based on our sample size, DEK protein is expressed in 100% of tumors of low malignant potential, 92% of tumors of low grade and in 71% of tumors of high grade. Next, we analyzed 42 urine samples from patients with active TCC, other malignant urogenital disease, non-malignant urogenital disease and healthy individuals for DEK protein expression by western blot analysis. We are the first to show that the DEK protein is present in the urine of bladder cancer patients. Approximately 84% of TCC patient urine specimens were positive for urine DEK.</p> <p>Conclusion</p> <p>Based on our pilot study of 38 bladder tumor tissue and 42 urine samples from patients with active TCC, other malignant urogenital disease, non-malignant urogenital disease and healthy individuals; DEK protein is expressed in bladder tumor tissue and voided urine of bladder cancer patients. The presence of DEK protein in voided urine is potentially a suitable biomarker for bladder cancer and that the screening for the presence of DEK protein in urine can be explored as a noninvasive diagnostic test for bladder cancer.</p

High Intensity Interval Training (HIIT) as a Potential Countermeasure for Phenotypic Characteristics of Sarcopenia: A Scoping Review

Background: Sarcopenia is defined as a progressive and generalized loss of skeletal muscle quantity and function associated predominantly with aging. Physical activity appears the most promising intervention to attenuate sarcopenia, yet physical activity guidelines are rarely met. In recent years high intensity interval training (HIIT) has garnered interested in athletic populations, clinical populations, and general population alike. There is emerging evidence of the efficacy of HIIT in the young old (i.e. seventh decade of life), yet data concerning the oldest old (i.e., ninth decade of life onwards), and those diagnosed with sarcopenic are sparse. Objectives: In this scoping review of the literature, we aggregated information regarding HIIT as a potential intervention to attenuate phenotypic characteristics of sarcopenia. Eligibility Criteria: Original investigations concerning the impact of HIIT on muscle function, muscle quantity or quality, and physical performance in older individuals (mean age ≥60 years of age) were considered. Sources of Evidence: Five electronic databases (Medline, EMBASE, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials [CENTRAL]) were searched. Methods: A scoping review was conducted using the Arksey and O'Malley methodological framework (2005). Review selection and characterization were performed by two independent reviewers using pretested forms. Results: Authors reviewed 1,063 titles and abstracts for inclusion with 74 selected for full text review. Thirty-two studies were analyzed. Twenty-seven studies had a mean participant age in the 60s, two in the 70s, and three in the 80s. There were 20 studies which examined the effect of HIIT on muscle function, 22 which examined muscle quantity, and 12 which examined physical performance. HIIT was generally effective in Improving muscle function and physical performance compared to non-exercised controls, moderate intensity continuous training, or pre-HIIT (study design-dependent), with more ambiguity concerning muscle quantity. Conclusions: Most studies presented herein utilized outcome measures defined by the European Working Group on Sarcopenia in Older People (EWGSOP). However, there are too few studies investigating any form of HIIT in the oldest old (i.e., ≥80 years of age), or those already sarcopenic. Therefore, more intervention studies are needed in this population

The role of atopy in otitis media with effusion among primary school children: audiological investigation

Objective of this study is to value the role of atopy in otitis media with effusion (OME) in children attending primary school in Western Sicily focusing on the audiological characteristics among atopic and non atopic subjects suffering from OME. 310 children (5-6 years old) were screened by skin tests and divided into atopics (G1) and non atopics (G2). The samples were evaluated for OME by pneumatic otoscopy, tympanogram and acoustic reflex tests. The parameters considered were: documented persistent middle ear effusion by otoscopic examination for a minimum of 3 months; presence of B or C tympanogram; absence of ipsilateral acoustic reflex and a conductive hearing loss greater than 25 dB at any one of the frequencies from 250 Hz through 4 kHz. 56 children (18.06%) resulted atopics while 254 were non atopics. OME was identified in 24 atopic children and in 16 non atopic children for a total number of 40 children; the overall prevalence rate was 12.9% (42.85% for G1 and 6.30% for G2). OME was bilateral in 28 children (70%), with a significative difference between G1 (79.17%) and G2 (56.25%). The prevalence of B tympanogram was 70.59%, corresponding to 79.07% for G1 and 56% for G2. The mean air conduction pure tone was respectively 31.97 dB for G1 and 29.8 dB for G2. The prevalence value of OME in atopics children, also supported by the higher predominance of bilaterality, B tympanogram and hearing loss among this group, could suggest the important role of allergy in the pathogenesis of OME

A genome-wide association study identifies protein quantitative trait loci (pQTLs)

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al

Deriving a mutation index of carcinogenicity using protein structure and protein interfaces

With the advent of Next Generation Sequencing the identification of mutations in the genomes of healthy and diseased tissues has become commonplace. While much progress has been made to elucidate the aetiology of disease processes in cancer, the contributions to disease that many individual mutations make remain to be characterised and their downstream consequences on cancer phenotypes remain to be understood. Missense mutations commonly occur in cancers and their consequences remain challenging to predict. However, this knowledge is becoming more vital, for both assessing disease progression and for stratifying drug treatment regimes. Coupled with structural data, comprehensive genomic databases of mutations such as the 1000 Genomes project and COSMIC give an opportunity to investigate general principles of how cancer mutations disrupt proteins and their interactions at the molecular and network level. We describe a comprehensive comparison of cancer and neutral missense mutations; by combining features derived from structural and interface properties we have developed a carcinogenicity predictor, InCa (Index of Carcinogenicity). Upon comparison with other methods, we observe that InCa can predict mutations that might not be detected by other methods. We also discuss general limitations shared by all predictors that attempt to predict driver mutations and discuss how this could impact high-throughput predictions. A web interface to a server implementation is publicly available at http://inca.icr.ac.uk/

A study of cleft lip/palate in a community in the South East of Ghana

The previous study in Wudoaba villages suggested that cleft lip and cleft palate (CL/CP) may be endemic in the Wudoaba cluster of villages in the Ketu South District of the Volta Region in South East Ghana. The study was to detect the prevalence of CL/CP in the Wudoaba communities and to investigate the factors associated with the causes of this malformation in the area. Two different interview-based questionnaires were designed to collect data over a period of 3 days from March 27 to 29, 2006. A purposive and accidental random sampling technique was used in the administering of the various questionnaires to the respondents. Data collected were recorded and analyzed with SPSS version 17.0. A total 99 respondents, with a mean age of 55.0 years, were interviewed. Out of it, 57.6% (n = 57) were related to their spouses: 54 first cousins and three other family relations. The prevalence of CL/CP is at least 6.3 per 1,000 people (i.e., 25/4,000). Majority (56.0%, n = 14) of the cleft cases were unilateral. Interviews revealed that genetic homogeneity and vitamin deficiencies in this community may be a causal factor for the high prevalence of CL/CP. This community provides clues suggesting that the magnitude of CL/CP may be larger than other studies and identifies the Wudoaba population as one that could be further studied to explore the underlying factors causing this congenital malformation

What are we measuring? A critique of range of motion methods currently in use for Dupuytren's disease and recommendations for practice

Background: Range of motion is the most frequently reported measure used in practice to evaluate outcomes. A goniometer is the most reliable tool to assess range of motion yet, the lack of consistency in reporting prevents comparison between studies. The aim of this study is to identify how range of motion is currently assessed and reported in Dupuytren’s disease literature. Following analysis recommendations for practice will be made to enable consistency in future studies for comparability. This paper highlights the variation in range of motion reporting in Dupuytren’s disease. Methods: A Participants, Intervention, Comparison, Outcomes and Study design format was used for the search strategy and search terms. Surgery, needle fasciotomy or collagenase injection for primary or recurrent Dupuytren’s disease in adults were included if outcomes were monitored using range of motion to record change. A literature search was performed in May 2013 using subject heading and free-text terms to also capture electronic publications ahead of print. In total 638 publications were identified and following screening 90 articles met the inclusion criteria. Data was extracted and entered onto a spreadsheet for analysis. A thematic analysis was carried out to establish any duplication, resulting in the final range of motion measures identified. Results: Range of motion measurement lacked clarity, with goniometry reportedly used in only 43 of the 90 studies, 16 stated the use of a range of motion protocol. A total of 24 different descriptors were identified describing range of motion in the 90 studies. While some studies reported active range of motion, others reported passive or were unclear. Eight of the 24 categories were identified through thematic analysis as possibly describing the same measure, ‘lack of joint extension’ and accounted for the most frequently used. Conclusions: Published studies lacked clarity in reporting range of motion, preventing data comparison and meta-analysis. Percentage change lacks context and without access to raw data, does not allow direct comparison of baseline characteristics. A clear description of what is being measured within each study was required. It is recommended that range of motion measuring and reporting for Dupuytren’s disease requires consistency to address issues that fall into 3 main categories:- Definition of terms Protocol statement Outcome reportin